Antiplatelet drugs are cornerstones in the prevention of heart attacks and strokes. Among them, clopidogrel and ticlopidine belong to a special group called thienopyridines.
What Are Thienopyridine Antiplatelet Drugs?
Thienopyridines are oral antiplatelet agents that:
- Inhibit platelet aggregation
- Prevent arterial thrombosis
- Reduce the risk of myocardial infarction and ischemic stroke
Common Drugs in This Class
- Ticlopidine (older)
- Clopidogrel (most commonly used)
- Prasugrel (newer, not discussed here)
Mechanism of Action (Very Important)
Both ticlopidine and clopidogrel act on the P2Y12 receptor on platelets.
Step-by-Step Mechanism
1. Drugs are converted to active metabolites in the liverExam-Friendly Line
Thienopyridines irreversibly inhibit ADP-induced platelet aggregation
Why ADP Inhibition Matters
ADP is a key substance that:
- Activates platelets
- Amplifies platelet aggregation
- Stabilizes thrombus formation
Blocking ADP = strong antiplatelet effect
Clopidogrel (Plavix)
Clopidogrel is the most widely prescribed antiplatelet drug after aspirin.
Key Characteristics
- Oral prodrug
- Irreversible P2Y12 inhibitor
- Once-daily dosing
- Safer than ticlopidine
Clinical Uses
- Acute coronary syndrome (ACS)
- Myocardial infarction (MI)
- Ischemic stroke prevention
- After coronary stent placement
- Aspirin intolerance
- Peripheral arterial disease
Dual Antiplatelet Therapy (DAPT)
Clopidogrel is commonly combined with:
- Aspirin
Ticlopidine (Ticlid)
Ticlopidine is the older drug of this class.
Why It Is Rarely Used Now
Although effective, ticlopidine causes serious adverse effects, making it less preferred.
Uses (Historical / Limited)
- Stroke prevention
- Coronary artery disease (rare today)
- Aspirin intolerance (earlier use)
Important Exam Point
Ticlopidine is largely replaced by clopidogrel due to safety concerns.
Comparison: Clopidogrel vs Ticlopidine
| Feature | Clopidogrel | Ticlopidine |
|---|---|---|
| Generation | Newer | Older |
| Safety | Better | Poor |
| Neutropenia | Rare | Common |
| TTP risk | Rare | Higher |
| Monitoring | Not routine | CBC required |
| Clinical use | Very common | Rare |
Pharmacokinetics (Simplified)
Clopidogrel
- Prodrug
- Activated by liver CYP enzymes (CYP2C19)
- Onset: 2–6 hours
- Duration: 7–10 days (platelet lifespan)
Ticlopidine
- Prodrug
- Slower onset
- Requires blood monitoring
Adverse Effects (High-Yield)
Common Side Effects (Both)
- Bleeding
- GI upset
- Rash
Serious Adverse Effects
Clopidogrel
- Bleeding
- Rare thrombotic thrombocytopenic purpura (TTP)
Ticlopidine (Exam Favorite)
- Neutropenia
- Agranulocytosis
- Aplastic anemia
- TTP
This toxicity is why ticlopidine is avoided
Contraindications
Avoid thienopyridines in:
- Active bleeding
- Recent hemorrhagic stroke
- Severe liver disease
Drug Interactions (Clopidogrel)
Important Interaction
Proton pump inhibitors (especially omeprazole)→ Reduce clopidogrel activation
Exam Tip
Pantoprazole is preferred if PPI is required.
Clopidogrel Resistance (Conceptual)
Some patients show reduced response due to:
- CYP2C19 genetic polymorphism
- Poor metabolic activation
This is why newer drugs (like prasugrel) were developed.
Clopidogrel vs Aspirin (Quick Comparison)
| Parameter | Clopidogrel | Aspirin |
|---|---|---|
| Mechanism | ADP receptor block | COX inhibition |
| Platelet inhibition | Strong | Moderate |
| GI irritation | Less | More |
| Asthma risk | None | Present |
Practical Clinical Points
- Effect lasts for entire platelet lifespan
- Stop clopidogrel 5–7 days before surgery
- No antidote available
- Platelet transfusion may help in bleeding
Exam-Oriented Memory Tricks
Drug Class
“P2Y12 blockers block platelet glue”
Toxicity
“Ticlo = Toxic”
(Neutropenia, agranulocytosis)
FAQs About Ticlopidine & Clopidogrel
1. What is the main mechanism of clopidogrel?
Clopidogrel irreversibly blocks the P2Y12 ADP receptor, preventing platelet aggregation.
2. Why is ticlopidine rarely used now?
Due to serious adverse effects like neutropenia and aplastic anemia.
3. Is clopidogrel better than aspirin?
Clopidogrel causes less gastric irritation and is used when aspirin is contraindicated.
4. What is dual antiplatelet therapy?
Combination of aspirin and clopidogrel, commonly used after coronary stenting.
5. Is clopidogrel reversible?
No, it irreversibly inhibits platelets for their entire lifespan.
6. Does clopidogrel need routine monitoring?
No routine monitoring is required in most patients.
7. What is a serious rare side effect of clopidogrel?
Thrombotic thrombocytopenic purpura (TTP).
8. Can clopidogrel be used in stroke?
Yes, it is widely used for ischemic stroke prevention.
9. Why is CYP2C19 important for clopidogrel?
It activates clopidogrel into its active metabolite.
10. Which drug is safer: ticlopidine or clopidogrel?
Clopidogrel is significantly safer and preferred.
